The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04522323




Registration number
NCT04522323
Ethics application status
Date submitted
22/07/2020
Date registered
21/08/2020

Titles & IDs
Public title
A Study to Evaluate MEDI5752 and Axitinib in Subjects With Advanced Renal Cell Carcinoma
Scientific title
A Phase 1b, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI5752 in Combination With Axitinib in Subjects With Advanced Renal Cell Carcinoma
Secondary ID [1] 0 0
2019-004338-41
Secondary ID [2] 0 0
D7980C00003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - MEDI5752
Treatment: Drugs - Axitinib
Treatment: Drugs - Lenvatinib

Experimental: Dose Exploration - The Dose exploration Phase is made up of Part A, B and Part C. Part A will evaluate the safety and tolerability of MEDI5752 in combination with Axitinib (2 patients), and Part B and C will evaluate the safety and tolerability of MEDI5752 in combination with Lenvatinib (\~72 patients)

Experimental: Dose Expansion - Evaluate safety and anti-tumor activity of MEDI5752 in combination with Lenvatinib (\~105 patients )


Treatment: Other: MEDI5752
MEDI5752

Treatment: Drugs: Axitinib
INLYTA

Treatment: Drugs: Lenvatinib
LENVIMA

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects experiencing adverse events (AEs)/serious adverse events (SAEs)
Timepoint [1] 0 0
Informed consent through 90-Day Post Last Dose.
Primary outcome [2] 0 0
Number of Participants With Dose Limiting Toxicities (DLT) of MEDI5752 and Lenvatinib (or Axitinib) during the Dose Exploration period.
Timepoint [2] 0 0
Informed consent through the first 21 days of treatment with MEDI5752 and Lenvatinib (or Axitinib) in the Dose Exploration Period.
Primary outcome [3] 0 0
Number of subjects experiencing adverse events (AEs) leading to discontinuation.
Timepoint [3] 0 0
Informed consent through 90-Day Post Last Dose.
Primary outcome [4] 0 0
Number of subjects experiencing abnormal laboratory evaluations.
Timepoint [4] 0 0
Informed Consent through 90 post treatment date.
Primary outcome [5] 0 0
Number of subjects experiencing changes in vital signs reported as Adverse Events.
Timepoint [5] 0 0
Informed consent through 90-Day Post Last Dose
Primary outcome [6] 0 0
Number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events.
Timepoint [6] 0 0
Informed consent through 90-Day Post Last Dose
Primary outcome [7] 0 0
Preliminary antitumor activity of MEDI5752 combined with Lenvatinib (or Axitinib) by Objective response rate per RECIST version (v) 1.1.
Timepoint [7] 0 0
First subject enrolled through 18 months from last subject enrolled, an average of 30 months.
Secondary outcome [1] 0 0
Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the progression free survival (PFS) according to RECIST v1.1.
Timepoint [1] 0 0
Last Subject Enrolled through study completion, an average of 48 months.
Secondary outcome [2] 0 0
Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Best Overall Response (BOR) according to RECIST v1.1.
Timepoint [2] 0 0
First subject enrolled through 18 months from last subject enrolled, an average of 30 months.
Secondary outcome [3] 0 0
Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Disease Control Rate (DCR).
Timepoint [3] 0 0
Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Secondary outcome [4] 0 0
Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Duration of Response (DOR) according to RECIST v1.1.
Timepoint [4] 0 0
Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Secondary outcome [5] 0 0
Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Time to Response (TTR) according to RECIST v1.1.
Timepoint [5] 0 0
Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Secondary outcome [6] 0 0
Pharmacokinetics of MEDI5752: Cmax
Timepoint [6] 0 0
Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle
Secondary outcome [7] 0 0
Pharmacokinetics of MEDI5752: AUC
Timepoint [7] 0 0
Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle
Secondary outcome [8] 0 0
Pharmacokinetics of MEDI5752: Cmin
Timepoint [8] 0 0
Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle
Secondary outcome [9] 0 0
Pharmacokinetics of MEDI5752: t 1/2
Timepoint [9] 0 0
Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle
Secondary outcome [10] 0 0
Pharmacokinetics of MEDI5752: Clearance
Timepoint [10] 0 0
Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle
Secondary outcome [11] 0 0
Immunogencity of MEDI572: Incidence of ADAs against MEDI5752
Timepoint [11] 0 0
Day 1, 8, 15, 22, 30, 64 and then Day 1 of every other cycle

Eligibility
Key inclusion criteria
* Age = 18 at the time of screening
* Body weight > 35 kg
* Written informed consent
* Histologically or cytologically proven advanced RCC with clear cell component
* Advanced RCC not previously treated in that setting
* Provision of tumor material (= 5 unstained slides or tissue block) from an archival or fresh tissue sample
* ECOG performance status of 0 or 1
* Subjects must have at least 1 measurable lesion according to RECIST v1.1
* Life expectancy = 12 weeks
* Adequate organ and marrow function
* Female subjects of childbearing potential must have negative pregnancy test at screening and prior to each administration of investigational product, and must use at least one highly effective method of contraception.
* Strongly recommend nonsterilized male partners of female subjects of childbearing potential use a male condom plus spermicide from screening to 7.6 months after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib.
Minimum age
18 Years
Maximum age
101 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
* Concurrent enrollment in another clinical study, unless it is an observational study.
* Previous treatment with mTOR inhibitors, PD-1, PD-L1, or CTLA-4 inhibitors for RCC or any other immune checkpoint inhibitor
* Previous treatment with VEGF inhibitors
* Evidence of the following infections: active infection including tuberculosis, human immunodeficiency virus, chronic or active hepatitis B or chronic or active hepatitis C
* History of organ transplant
* Active or prior documented autoimmune or inflammatory disorders
* Current or prior use of immunosuppressive medication within 14 days prior to the first dose of investigational product.
* Poorly controlled blood pressure (BP) defined as systolic BP = 140/90 mmHg at screening and not able to be controlled prior to Cycle 1 Day 1 and any change in antihypertensive medications within 1 week prior to Cycle 1 Day 1.
* Thromboembolic (arterial or venous) events within previous 6 months
* Any concurrent therapy for cancer
* Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product
* Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s)
* Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord compression
* History of another primary malignancy
* Unresolved toxicities from previous anticancer therapy
* Major surgery within 4 weeks prior to enrollment or radiation therapy within 2 weeks prior to enrollment or has not recovered from AEs due to prior treatment
* Female subjects must not breastfeed and must not donate, or retrieve for their own use, ova from screening to 3 months after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib.
* History of arrhythmia which is symptomatic or requires treatment, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
* Uncontrolled intercurrent illness within the last 6 months prior to enrollment
* Clinically significant gastrointestinal abnormality
* Serious nonhealing wound, ulcer, or bone fracture
* Has clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks before the first dose of investigational product
* Radiographic evidence of major blood vessel invasion/infiltration/encasement

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Frankston
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment hospital [3] 0 0
Research Site - Waratah
Recruitment postcode(s) [1] 0 0
3199 - Frankston
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
France
State/province [10] 0 0
Villejuif Cedex
Country [11] 0 0
Spain
State/province [11] 0 0
Barcelona
Country [12] 0 0
Spain
State/province [12] 0 0
Córdoba
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid
Country [14] 0 0
Spain
State/province [14] 0 0
Sabadell
Country [15] 0 0
Spain
State/province [15] 0 0
Sevilla
Country [16] 0 0
Spain
State/province [16] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
MedImmune LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AstraZeneca Early Oncology
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Available to whom?
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.